Abnormal respiratory control has been cited as a possible cause of death of infants dying from the Sudden Infant Death Syndrome (SIDS). It has been suggested that delayed maturation of control mechanisms in the central nervous system (CNS) contribute to the pathophysiology of SIDS since the frequency of death is greatest during the second to fifth month of life and is higer in premature and/or low birth weight babies. We propose that adenosine receptors located in the medulla and pons, two recognized centers of CNS respiratory control, are involved in this control, and that abnormalities in receptor number and/or kinetic parameters may reflect delayed maturation of the system. This study will include animal models and postmortem specimens of SIDS and non-SIDS. It is known that the adenosine agonist phenylisopropyl adenosine (PIA) causes apnea, decreased respiration, and death; furthermore, young rabbits are susceptible to death from PIA at a five-fold lower concentration than older animals. Theophylline, an antagonist of adenosine receptors, prevents both the PIA stimulated apnea in an animal model as well as clinical apnea in humans. Additional links between adenosine and respiration have been reported: 1) a rapid rise in adenosine levels occurs during hypoxemia and hypercapnia, especially in the medulla and pons, and 2) there is an elevated blood level of hypoxanthine, a breakdown product of adenosine, during hypoxemia. The rapid rise in adenosine level during hypoxemia may also suggest a possible role of adenosine in the depression of respiration in neonates observed 3 or 4 minutes after they are exposed to hypoxia. Animal models are proposed to study the role of adenosine receptors in the control of respiration and its relationship to SIDS. One model will utilize rats with experimentally elevated adenosine receptors due to chronic exposure to adenosine antagonists. The resultant effect on respiration will be determined in responses to challenges of hypoxia, PIA and theophylline. The second model will determine the effect of chronic stress (hypoxemia) on the ontogeny and function of adenosine receptors in the rat brain, especially in the medulla and pons. The results of the animal studies will be correlated with post-mortem studies on SIDS victims and control subjects by determination of adenosine receptor density, binding parameters, and ontogeny using membrane preparations as well as in situ autoradiography of brain stem sections.